The key to Genzyme Corp.’s move to withdraw its leukemia drug, Campath, in anticipation of a multiple sclerosis indication seems to be working with the cancer community and establishing generous patient support.

Genzyme, the rare disease unit of Sanofi, is in the process of removing the Campath brand of alemtuzumab from commercial availability in about 50 markets, including the United States and the European Union – and the company has been transparent about its reasoning. It does not want Campath to be used off label in the multiple sclerosis setting when a lower-dose formulation of alemtuzumab obtains approval for multiple sclerosis.

But instead of courting controversy with the potentially contentious business decision, the firm has decided to make Campath available free of charge under a patient-access program. The leukemia treatment had reportedly cost in the range of $50,000-$60,000.

In an Aug. 9 letter to health care providers, Genzyme makes clear that it will stop selling Campath, not "for any reasons related to product safety, efficacy or supply, but as part of the company’s plan for bringing alemtuzumab forward as a treatment for a new indication." The company added that it "will continue manufacturing sufficient quantities of alemtuzumab to supply this patient access program."

Although sacrificing one patient community (and cancer, at that) in favor of a more lucrative one certainly seems as if it could provoke controversy, the steps Genzyme took appear to be enough to ease the company past public outcry.

Hildy Dillon, senior vice president of patient services for the Leukemia and Lymphoma Society, said that her organization was concerned when it first learned of Sanofi/Genzyme’s plans to stop selling Campath, but added that the companies had done a strong job of laying the groundwork for a transition from commercial product to one available for free under a compassionate-use protocol.

"There is an extensive patient-distribution system which they have shared with us," she said in an interview. "They’ve actually been quite supportive to us and our constituents by telling us what the distribution is and how they have communicated their plans to health care providers who treat our patients – hematology oncologists both in the community and in the major cancer centers.

"[Those doctors] are now aware of how they can access the drug since they no longer will be purchasing it, but they can contact the company directly to get whatever supply they need."

Campath Available to New Patients

Ms. Dillon said the Leukemia and Lymphoma Society was assured that Campath will be available for all patients who need it, including those who may be prescribed it for the first time after it is no longer available commercially.

"Genzyme was in touch with advocacy groups like ours to make sure we were aware of the change and how physicians will be accessing the drug," she said. "They’ve done a lot in their due diligence to inform both the physician community and the patients. ... It’s our understanding that there won’t be any shortage of supply and that the patients who need Campath will be able to get it."

By making it harder for alemtuzumab to be used in the MS setting off label, Genzyme also increases its chances of making the product (to be marketed as Lemtrada in the MS indication) much more lucrative. Campath, an anti-CD52 monoclonal antibody indicated for the treatment of chronic lymphocytic leukemia (CLL), yielded net sales of $76 million last year for Sanofi. The French pharmaceutical company bought out Genzyme for about $19.4 billion in early 2011, largely on the strength of the biotech company’s success in developing large-molecule products for rare disorders.

Industry analysts predict much bigger sales for Lemtrada, which will be provided in a 12-mg dose per treatment, compared with 30 mg for Campath. A supplemental Biologics License Application was filed at the Food and Drug Administration this past June, with a marketing authorization application sent to the European Medicines Agency in the same time frame, which means that regulatory decisions on Lemtrada are anticipated during the second quarter of 2013. Analysts widely predict initial-review approvals by the FDA and the EMA, a launch in late 2013, and the ramp-up to sales ranging between $336 million and $400 million in 2016.

No Similarity to Genentech AMD Dilemma, Genzyme Says

Sanofi/Genzyme’s dilemma regarding what to do with a useful but modestly selling drug that offers the potential to earn more in a second indication mirrors in some ways the challenge faced by Roche/Genentech Inc. with its vascular endothelial growth factor therapies Lucentis (ranibizumab) and Avastin (becavizumab). Both demonstrated potential in clinical trials for the treatment of wet age-related macular degeneration, but Roche never filed Avastin for AMD because it would undercut the Lucentis market in that indication. Lucentis costs about $2,000 per injection, while oncology drug Avastin is available in small-dose syringes for between $35 and $50 per unit.

A Genzyme spokesperson denied the similarity between the two business cases, however. "We believe the situation that we are managing with alemtuzumab is unique," he said in an e-mail exchange.

Sanofi/Genzyme made its decision on withdrawing Campath gradually, and consulted the MS and oncology communities, including patient advocacy groups, along the way, the spokesperson added.

"We are changing the way Campath is made available for its current use because we have decided to focus on bringing alemtuzumab forward for MS, where it holds the potential to address a significant unmet need," he said. "Importantly, this step will also help ensure that the product is used for MS patients only within the clinical trial setting prior to approval, given the differences in dosing and safety profile associated with its use in CLL and MS."

Because Lemtrada is a lower dosage of alemtuzumab than is Campath, it has a different safety profile. The MS space offers multiple therapeutic options, but each – including Lemtrada, if approved – poses potential safety issues.

Biogen Idec Inc. and Elan Corp. continually have battled reports of progressive multifocal leukoencephalopathy (PML) in patients treated with their drug, Tysabri (natalizumab), which claimed 12% of the MS market in 2011, garnering sales of $1.5 billion. Sales have picked up in recent months now that patients can use a diagnostic to predict their risk for PML.

Novartis AG markets a once-daily oral drug for MS, Gilenya (fingolimod), which launched in 2011, claiming a 4% share of the market and sales of $494 million. That product, however, sometimes presents cardiovascular side effects.

In a pivotal trial testing alemtuzumab in relapsed, remitting MS, Sanofi/Genzyme found that 15.9% of treatment-arm patients experienced autoimmune-related thyroid adverse events, compared with just 5% of control-arm patients who received Roche’s Rebif (interferon beta-1a). Meanwhile, 0.9% of the alemtuzumab recipients developed immune thrombocytopenia over a 2-year treatment period.

Genzyme, which has a management program in place to detect and treat both types of adverse events, says that even higher rates of autoimmune effects have been seen in MS testing with the antibody, but more than 90% of such cases are mild to moderate in severity and are treatable with standard therapies. At the 30-mg dosage used for CLL, the Campath label includes warnings for risk of cytopenia, infections, and infusion reactions.

Dosing, Efficacy Advantages Expected in MS

Dosing and efficacy both are expected to give Lemtrada a potential leg up in the MS space. Lemtrada would be dosed much less frequently than other MS drugs, although it would not offer the convenience of oral availability presented by Gilenya. An intravenous infusion drug, Lemtrada would be dosed at 12 mg for 5 consecutive days during the first year of treatment and then for 3 consecutive days the following year.

In the CARE-MS II trial, alemtuzumab reversed disability in nearly one-third of patients whose disease had relapsed while they received other therapy. Top-line data showed a 49% reduction in relapse rate, compared with patients treated with Rebif, along with a 42% reduction in worsening of disability. Longer-term data from the trial showed a reduction in disability, as measured by the Expanded Disability Status Scale, for treatment-arm patients, whereas control-arm patients saw increased disability.

In December 2010, while the Sanofi acquisition of Genzyme was being negotiated, Genzyme offered projections that Lemtrada would achieve 5% market share in its launch year, moving up to 10% and 12% in years 2 and 3 on the market, and an 18%-20% share by year 5. At that time, then–Genzyme executive Mark Enyedy acknowledged concerns "about managing the use of the oncology product in MS" and talked of a range of solutions, which included pulling Campath from commercialization.

Perhaps the most bullish on Lemtrada’s market potential is Stephen McGarry, an analyst with Société Générale Cross Asset Research. He projects Lemtrada’s reaching 472 million euros in sales by 2016 and continuing to grow, peaking at 1.134 billion euros in 2020. "Although we view the side effect profile as a negative relative to competing drugs in the MS space, and its route of administration is not oral, which is also a potential disadvantage, the dosing frequency and high level of efficacy more than balance those concerns in our view," he wrote in an Aug. 9 note.

Sanofi has another MS candidate, Aubagio (teriflunomide), pending at the FDA with a Sept. 12 action date. It plans to position Aubagio, an oral pill, as a convenient therapy for patients in early stages of MS, whereas Lemtrada would be targeted to those with more serious, later-stage disease.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

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